I propose that the intracellular Ca ions concentration of the erythrocyte is regulated by means of a sequence of events that involves several membrane-bound enzymes. This sequence is as follows. As a result of the influence of a membrane-bound protein kinase upon a membrane-bound phosphatidylinositol kinase or upon a membrane-bound phosphatidylinositol phosphate phosphatase, or upon both, the concentration of membrane-associated phosphatidylinositol phasphates is increased. This increase, in turn, enhances the activity of the membrane-bound Ca ions -Mg ions -dependent ATPase. This increased activity of the Ca ions -Mg ions -dependent ATPase promotes the expulsion of Ca ions from the erythrocyte thus allowing the appropriate intracellular concentration of this cation to be maintained. This proposal is being examined in our laboratory by means of isolating and purifying the enzymes thought to be involved and, subsequently, determining the influence of each of the proposed modulators upon the kinetic parameters of the appropriate enzymatic reaction. Specifically, we are determining the extent to which the protein kinase can perturb the kinetic parameters of the reactions catalyzed by the phosphatidylinositol kinases and those catalyzed by the phosphatidylinositol phosphate phosphatases and, also, the extent to which the phosphatidylinositol phosphates can perturb the kinetic parameters of the reaction catalyzed by the Ca ions -Mg ions -dependent ATPase. It is felt that this direct approach offers the best opportunity for obtaining the data under the most carefully controlled conditions. It is also felt that these data, once obtained, will provide valuable insight into the particular regulatory process concerned as well as into other regulatory processes that occur in certain cell membranes.